One major aspect in studying stress responses is their highly transient nature, typically lasting several hours with chronic activation leading to compensation and cell death. Thus, to investigate acute responses to unfolded mitochondrial proteins, we utilize chemical inhibitors that rapidly induce protein misfolding to allow a time-resolved study of the resulting signaling and cellular modulation. Using these tools, we recently defined the acute transcriptional mtUPR and discovered a novel mtUPR axis leading to a decrease in mitochondrial RNA processing and translation. This pathway provides with an additional approach to restore mitochondrial (and cellular) proteostasis.